We propose to exploit the recent explosion of structural data that has recently become available on the Vitamin K-dependent coagulation proteins by utilizing theoretical techniques to a) complete the structures where domains or loops are missing, b) test the models by performing simulations on variant proteins of human disease importance, and c) to model activation complexes on Factor VIIa/Tissue Factor with Factor IX and X. The key structural sets that now exist are partial structures for Factor Xa, IXa, Protein Ca (The EGF and catalytic domains), the Gla and first Kringle domains of pro-thrombin (Factor II) (as well as a number of structures of inhibited complexes of thrombin), and the almost complete structure of factor VIIa complexed to soluble Tissue Factor. The first of these structures was published in 1992. An essential component of our confidence that the bulk of these studies can be successfully addressed is the recent advanced in simulation technology of the Particle Mesh Ewald method (PME). This development, which took place in our collaboration with T. Darden (NIEHS, RTP, NC), makes possible the accurate computation of the ion-ion interactions; PME is rapidly being implemented into a number of simulation codes around the world. The planned research is thus an integration of experiment and theory to gain complete pictures of the structure and functions of the Vitamin K-dependent coagulation proteins. The complete solvated structures developed will be made available on the internet web and will retain value as new experimental structures become available.